Compositions and methods for treatment of bone associated diseases

Abstract

Mutant M-CSF protein, comprising α v β 3 integrin binding motif and pharmaceutical compositions comprising same, are provided. Further, use of the composition for the treatment and or prevention of diseases associated with increased bone resorption are provided.

The invention claimed is: 
     
       1. A polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 16, and SEQ ID NO: 19,
 wherein said polypeptide is characterized by antagonizing c-FMS and/or impairing osteoclast differentiation, and 
 wherein said polypeptide may be further characterized by having diminished non-covalent dimerization. 
 
     
     
       2. The polypeptide of  claim 1 , wherein said polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 16 and SEQ ID NO: 19, and wherein residues 25-32 of said SEQ ID NO: 16 or SEQ ID NO: 19 is an RGD motif selected from the group consisting of: SEQ ID NO: 8 (QTRGDSPS), SEQ ID NO: 9 (TYPRGDMCS), and SEQ ID NO: 10 (EPVRGDNIN). 
     
     
       3. An isolated nucleic acid molecule encoding the polypeptide of  claim 1 . 
     
     
       4. An expression vector comprising the nucleic acid of  claim 3 . 
     
     
       5. A cell transformed or transfected with the expression vector of  claim 4 . 
     
     
       6. A pharmaceutical composition comprising the polypeptide of  claim 1  and a pharmaceutical acceptable carrier. 
     
     
       7. A method for treating a disease characterized by excessive osteoclast differentiation or increased bone resorption in a subject in need thereof, the method comprising the step of administering to said subject a therapeutically effective amount of a pharmaceutical composition comprising the polypeptide of  claim 1  and a pharmaceutical acceptable carrier, thereby treating a disease characterized by excessive osteoclast differentiation or increased bone resorption in a subject in need thereof. 
     
     
       8. The method of  claim 7 , wherein said disease associated with increased bone resorption is osteoporosis.